Systemic immune dysregulation in severe tuberculosis patients revealed by a single-cell transcriptome atlas. Issue 5 (May 2023)

• Record Type: Journal Article
• Authors: Wang, Yi; Sun, Qing; Zhang, Yun; Li, Xuelian; Liang, Qingtao; Guo, Ru; Zhang, Liqun; Han, Xiqin; Wang, Jing; Shao, Lingling; Xue, Yu; Yang, Yang; Li, Hua; Nie, Lihui; Shi, Wenhui; Liu, Qiuyue; Zhang, Jing; Duan, Hongfei; Huang, Hairong; Luu, Laurence Don Wai; Tai, Jun; Yang, Xinting; Wang, Guirong
• Is Part Of: Journal of infection. Volume 86:Issue 5(2023)
• Page Start: 421
• Page End: 438
• Publication Date: 2023-05
• Subjects: Tuberculosis -- Mycobacterium tuberculosis -- ScRNA-seq -- Severe patients -- Immunological responses -- Cytokine storm; Tuberculosis TB -- Mycobacterium tuberculosis Mtb -- Latent TB infection TBI -- Intensive care unit ICU -- Peripheral blood mononuclear cells PBMCs -- B cell receptor BCR -- T cell receptor TCR; Infection -- Periodicals; Bacterial Infections -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.905
• DOI: 10.1016/j.jinf.2023.03.020
• Languages: English
• ISSNs: 0163-4453

Abstract

Summary: Tuberculosis (TB), caused by Mycobacterium tuberculosis ( Mtb ) infection, is currently the deadliest infectious disease in human that can evolve to severe forms. A comprehensive immune landscape for Mtb infection is critical for achieving TB cure, especially for severe TB patients. We performed single-cell RNA transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing of 213, 358 cells from 27 samples, including 6 healthy donors and 21 active TB patients with varying severity (6 mild, 6 moderate and 9 severe cases). Two published profiles of latent TB infection were integrated for the analysis. We observed an obviously elevated proportion of inflammatory immune cells (e.g., monocytes), as well as a markedly decreased abundance of various lymphocytes (e.g., NK and γδT cells) in severe patients, revealing that lymphopenia might be a prominent feature of severe disease. Further analyses indicated that significant activation of cell apoptosis pathways, including perforin/granzyme-, TNF-, FAS- and XAF1-induced apoptosis, as well as cell migration pathways might confer this reduction. The immune landscape in severe patients was characterized by widespread immune exhaustion in Th1, CD8 + T and NK cells as well as high cytotoxic state in CD8 + T and NK cells. We also discovered that myeloid cells in severe TB patients may involve in the immune paralysis. Systemic upregulation of S100A12 and TNFSF13B, mainly by monocytes in the peripheral blood, may contribute to the inflammatory cytokine storms in severe patients. Our data offered a rich resource for understanding of TB immunopathogenesis and designing effective therapeutic strategies for TB, especially for severe patients. Graphical Abstract: ga1 Highlights: A detailed immune landscape of TB was depicted by a single-cell transcriptome atlas. Lymphopenia is one prominent feature of severe TB patients, causing by cell apoptosis and migration. Severe TB is characterized by widespread immune exhaustion in Th1, CD8 + T and NK cells S100A12 and TNFSF13B, mainly secreted by monocytes, are response for cytokine storms in severe TB patients.